This invention relates to a process for oxidizing amino secondary alcohols to corresponding ketones. More particularly, the invention pertains to the conversion of guinine, or derivatives thereof, to quininone in high yield, with a substantial absence of by-products and impurities. The invention concerns a process which dispenses with the conventional use of alcoholates according to modified Oppenhauer methods.
Various methods for the conversion of the cinchona alkaloids to corresponding ketones, and in particular methods for the oxidation of quinine to quininone, are known in the art. One of the earliest methods concerned the use of acidic reagents, e.g., chromic acid, to achieve such an oxidation, but the yield of quininone was so small as to make it impractical for most uses (see, Rabe, P., et al., Ann., 364, 346 (1909)). In 1945, Woodward, et al., (Woodward, R. B., et al., J. Am. Chem. Soc., 67, 1425 (1945)) attempted the use of the Oppenhauer method to effect oxidation of quinine, but upon finding that the use of the conventional aluminum alcoholate as a catalyst was ineffective in achieving the desired conversion, they modified the Oppenhauer method by using potassium t-butylate as the catalyst. They were able to achieve a quantitative oxidation by boiling quinine along with the alkoxide catalyst and benzophenone in benzene. Warnhoff et al suggested later (Warnhoff, E. W., et al., J. Org. Chem., 28, 1431 (1963)) that the quinine to quininone conversion would proceed more rapidly if the hydride acceptor was fluorenone in benzene instead of the benzophenone used by Woodward, et al.
In all of these methods of recent years, one common theme is found in the use of an alkoxide catalyst to achieve the desired oxidation reaction. While these processes have been effective in achieving an acceptable yield of quininone, since alcoholates are used, they enter into the reaction causing the formation of a number of by-products and impurities which must ultimately be removed by expensive purification treatments.
By means of the present invention, the problems generated by the prior art processes have been resolved since it is no longer necessary to employ alcoholates in the oxidation of quinine or its derivatives to quininone.